Transplant

Question 1

Define autologous

Answer 1

“self”

Question 2

Define allogeneic

Answer 2

“person to person”

Question 3

Define xenogeneic

Answer 3

“across species”

Question 4

Define hyperacute rejection

Answer 4

Robust reaction that occurs within minutes (major barrier to xenotransplantation, not common in clinical transplant)

Question 5

Define acute rejection

Answer 5

Occurs within days to weeks in non-immune suppressed individuals or months to years in suppressed pts

**can be cellular or humoral in nature (T cell or Ab mediated)

Question 6

Define chronic rejection

Answer 6

Occurs months to years after transplant (now the major cause of graft failure)

Characterized by:

• vascular changes
• intersitital fibrosis
• loss of renal parenchyma -> renal ischemia
• interstitial fibrosis
• tubular atrophy

Question 7

Define chimerism

Answer 7

Mixture of donor and self

Question 8

What are transplantation antigens?

Answer 8

Human leukocyte antigen (HLA; another name for the human MHC molecules)

*For hematopoietic stem cell grafts, “minor” histocompatibility antigens can be targets

Question 9

What are the MHC alleles?

Answer 9

6 class I MHC alleles

6 class II MHC alleles
(HLA-DR, HLA-DQ, HLA-DP; 3 from each parent)

(HLA-A, HLA-B, and HLA-C; 3 from each parent)

Question 10

How are MHC proteins matched for transplant?

Answer 10

All MHC proteins can be targets for rejection, but HLA-C and HLA-DP are less important

*Many types of organ transplants no longer MHC match because of the ability to suppress the immune system with drugs

**Matching is still important for hematopoietic stem cell transplants

Question 11

What is the difference between direct and indirect alloantigen recognition?

Answer 11

Direct= Alloreactive T cell recognizes allogenic MHC (regardless of antigen being presented) on allogenic APC that was transferred in the transplant

Indirect= Recipient APC recognizes foreign MHC on allogenic APC, phagocytoses it, degrades and presents on self MHC to alloreactive T cell (foreign processed peptide recognized)

Question 12

What is the MOA of cyclosporine graft rejection prevention?

Answer 12

Blocks T cell cytokine production by inhibiting the phosphatase calcineurin and thus blocking activation of the NFAT transcription factor

Question 13

What are the sources of HSCs?

Answer 13

Hematopoietic stem cells

Historically obtained from bone marrow

Also from peripheral blood (after mobilization by growth factors/chemokine receptor inhibitors) or cord blood

Question 14

With HSCT, can graft rejection or graft versus host occur?

Answer 14

In hematopoietic stem cell transplant, BOTH host-anti-donor (graft rejection) and donor-anti-host rejection (graft vs host disease) can occur

Question 15

What are minor histocompatibility antigens (miHA)?

Answer 15

Less potent “minor” antigens that can induce rejection; cleaved and processed endogenous proteins that occupy the binding groove of MHC class I and II molecules

*Genetic polymorphism= principal determinant whether a self peptide can be a miHA; majority due to SNPs

**cumulative; multiple miHAs=major

Question 16

What are some of the immune problems associated with transplant of allogenic HSCs?

Answer 16

• finding a suitable donor (histocompatiblity)
• graft vs host disease
• risk for infection (immune deficiency before WBCs return to normal)
• graft rejection
• malignant disease relapse
• slow immune recovery (esp for older patients)

Question 17

How is graft vs host disease classified?

Answer 17

Given a grade (I being least severe, IV being most severe) based on the extent of involvement of key target tissues such as skin, liver, and GI

Question 18

What drives GVHD?

Answer 18

Driven by donor T cells

**a bigger problem than recipient-anti-donor rejection

Question 19

What type of rejection is predominant in solid organ transplant? What type of antigen drives this rejection?

Answer 19

Recipient-anti-donor

Acute driven by recipient T cells (can involve B cells/Abs)
Chronic rejection can involve CD4 T cells and B cells

**MHC (major) drives rejection, minor HAs not as important

Question 20

What type of antigen drives rejection in HSCT?

Answer 20

Both major (MHC) and minor HAs (miHA) play important roles in alloreactivity with stem cells

*recall in solid organ MHC drives rejection